A selective increase in Fos expression in spinal dorsal horn neurons following graded thermal stimulation in rats with experimental mononeuropathy

In order to clarify the central mechanisms of thermal hyperalgesia produced by peripheral nerve injury, Fos protein-like immunoreactive (Fos-LI) cells in spinal dorsal horn neurons were studied in rats with chronic constriction nerve injury (CCI) following graded thermal stimulation of the hind paw. The graded thermal stimuli (cold: 5, 10 and 15°C, heat: 42, 46 and 54°C) were applied to the planter surface of the operated hind paw 14 days after CCI or sham operation, and the number of Fos-LI cells in the spinal dorsal horn was quantified. Many Fos-LI cells were expressed in the superficial laminae of the spinal dorsal horn both in sham-operated and CCI rats following thermal stimulation. Fos-LI cells were mainly restricted to the medial half of the superficial laminae of the spinal dorsal horn, and were sparsely distributed in the deeper laminae. The number of Fos-LI cells in the superficial laminae (laminae I–II) of the dorsal horn was significantly higher in CCI rats after stimulation at 10 and 46°C, but not at the other stimulating temperatures (5, 15, 42, and 54°C) as compared to that in sham-operated rats. In laminae III–IV, the number of Fos-LI cells was significantly higher at all stimulus temperatures in CCI rats when compared to the sham-operated rats. No distribution difference of Fos-LI cells was observed between CCI and sham-operated rats in laminae V–VI. Thus, in the spinal dorsal horn of the CCI rats, there was a selective increase in thermal stimulus-induced Fos-LI cells in the superficial dorsal horn after stimulating at near noxious threshold intensities and a non-selective increase in Fos-LI cells in laminae III-IV after both noxious and innocuous thermal stimuli. The increase of Fos-LI cells in the superficial laminae may be related to hypersensitivity to noxious stimuli while the increase of Fos-LI cells in laminae III–IV may be related to an increased sensitivity to both noxious and innocuous stimuli that leads to increased reflex activity following nerve injury.